Comparison of different methods for the calculation of the microvascular flow index

The microvascular flow index (MFI) is commonly used to semiquantitatively characterize the velocity of microcirculatory perfusion as absent (0), intermittent (1), sluggish (2), or normal (3). There are three approaches to compute MFI: (1) the average of the predominant flow in each of the four quadrants (MFI by quadrants), (2) the direct assessment during the bedside video acquisition (MFI point of care), and (3) the mean value of the MFIs determined in each individual vessel (MFI vessel by vessel). We hypothesized that the agreement between the MFIs is poor and that the MFI vessel by vessel better reflects the microvascular perfusion. For this purpose, we analyzed 100 videos from septic patients. In 25 of them, red blood cell (RBC) velocity was also measured. There were wide 95% limits of agreement between MFI by quadrants and MFI point of care (1.46), between MFI by quadrants and MFI vessel by vessel (2.85), and between MFI by point of care and MFI vessel by vessel (2.56). The MFIs significantly correlated with the RBC velocity and with the fraction of perfused small vessels, but MFI vessel by vessel showed the best R 2. Although the different methods for the calculation of MFI reflect microvascular perfusion, they are not interchangeable and MFI vessel by vessel might be better.Facultad de Ciencias Médica

Central venous minus arterial carbon dioxide pressure to arterial minus central venous oxygen content ratio as an indicator of tissue oxygenation: a narrative review

The central venous minus arterial carbon dioxide pressure to arterial minus central venous oxygen content ratio (Pcv-aCO2/Ca-cvO2) has been proposed as a surrogate for respiratory quotient and an indicator of tissue oxygenation. Some small observational studies have found that a Pcv-aCO2/Ca-cvO2 > 1.4 was associated with hyperlactatemia, oxygen supply dependency, and increased mortality. Moreover, Pcv-aCO2/Ca-cvO2 has been incorporated into algorithms for tissue oxygenation evaluation and resuscitation. However, the evidence for these recommendations is quite limited and of low quality. The goal of this narrative review was to analyze the methodological bases, the pathophysiologic foundations, and the experimental and clinical evidence supporting the use of Pcv-aCO2/Ca-cvO2 as a surrogate for respiratory quotient. Physiologically, the increase in respiratory quotient secondary to critical reductions in oxygen transport is a life-threatening and dramatic event. Nevertheless, this event is easily noticeable and probably does not require further monitoring. Since the beginning of anaerobic metabolism is indicated by the sudden increase in respiratory quotient and the normal range of respiratory quotient is wide, the use of a defined cutoff of 1.4 for Pcv-aCO2/Ca-cvO2 is meaningless. Experimental studies have shown that Pcv-aCO2/Ca-cvO2 is more dependent on factors that modify the dissociation of carbon dioxide from hemoglobin than on respiratory quotient and that respiratory quotient and Pcv-aCO2/Ca-cvO2 may have distinct behaviors. Studies performed in critically ill patients have shown controversial results regarding the ability of Pcv-aCO2/Ca-cvO2 to predict outcome, hyperlactatemia, microvascular abnormalities, and oxygen supply dependency. A randomized controlled trial also showed that Pcv-aCO2/Ca-cvO2 is useless as a goal of resuscitation. Pcv-aCO2/Ca-cvO2 should be carefully interpreted in critically ill patientsFacultad de Ciencias Médica

Comparison of different methods for the calculation of the microvascular flow index

The microvascular flow index (MFI) is commonly used to semiquantitatively characterize the velocity of microcirculatory perfusion as absent (0), intermittent (1), sluggish (2), or normal (3). There are three approaches to compute MFI: (1) the average of the predominant flow in each of the four quadrants (MFI by quadrants), (2) the direct assessment during the bedside video acquisition (MFI point of care), and (3) the mean value of the MFIs determined in each individual vessel (MFI vessel by vessel). We hypothesized that the agreement between the MFIs is poor and that the MFI vessel by vessel better reflects the microvascular perfusion. For this purpose, we analyzed 100 videos from septic patients. In 25 of them, red blood cell (RBC) velocity was also measured. There were wide 95% limits of agreement between MFI by quadrants and MFI point of care (1.46), between MFI by quadrants and MFI vessel by vessel (2.85), and between MFI by point of care and MFI vessel by vessel (2.56). The MFIs significantly correlated with the RBC velocity and with the fraction of perfused small vessels, but MFI vessel by vessel showed the best R 2. Although the different methods for the calculation of MFI reflect microvascular perfusion, they are not interchangeable and MFI vessel by vessel might be better.Facultad de Ciencias Médica

Venoarterial PCO₂-to-arteriovenous oxygen content difference ratio is a poor surrogate for anaerobic metabolism in hemodilution: an experimental study

Background: The identification of anaerobic metabolism in critically ill patients is a challenging task. Observational studies have suggested that the ratio of venoarterial PCO2 (Pv–aCO2) to arteriovenous oxygen content difference (Ca–vO2) might be a good surrogate for respiratory quotient (RQ). Yet Pv–aCO2/Ca–vO2 might be increased by other factors, regardless of anaerobic metabolism. At present, comparisons between Pv–aCO2/Ca–vO2 and RQ have not been performed. We sought to compare these variables during stepwise hemorrhage and hemodilution. Since anemia predictably produces augmented Pv–aCO2 and decreased Ca–vO2, our hypothesis was that Pv–aCO2/Ca–vO2 might be an inadequate surrogate for RQ. Methods: This is a subanalysis of a previously published study. In anesthetized and mechanically ventilated sheep (n = 16), we compared the effects of progressive hemodilution and hemorrhage by means of expired gases analysis. Results: There were comparable reductions in oxygen consumption and increases in RQ in the last step of hemodilution and hemorrhage. The increase in Pv–aCO2/Ca–vO2 was higher in hemodilution than in hemorrhage (1.9 ± 0.2 to 10.0 ± 0.9 vs. 1.7 ± 0.2 to 2.5 ± 0.1, P < 0.0001). The increase in Pv–aCO2 was lower in hemodilution (6 ± 0 to 10 ± 1 vs. 6 ± 0 to 17 ± 1 mmHg, P < 0.0001). Venoarterial CO2 content difference and Ca–vO2 decreased in hemodilution and increased in hemorrhage (2.6 ± 0.3 to 1.2 ± 0.1 vs. 2.8 ± 0.2 to 6.9 ± 0.5, and 3.4 ± 0.3 to 1.0 ± 0.3 vs. 3.6 ± 0.3 to 6.8 ± 0.3 mL/dL, P < 0.0001 for both). In hemodilution, Pv–aCO2/Ca–vO2 increased before the fall in oxygen consumption and the increase in RQ. Pv–aCO2/Ca–vO2 was strongly correlated with Hb (R2 = 0.79, P < 0.00001) and moderately with RQ (R2 = 0.41, P < 0.0001). A multiple linear regression model found Hb, RQ, base excess, and mixed venous oxygen saturation and PCO2 as Pv–aCO2/Ca–vO2 determinants (adjusted R2 = 0.86, P < 0.000001). Conclusions: In hemodilution, Pv–aCO2/Ca–vO2 was considerably increased, irrespective of the presence of anaerobic metabolism. Pv–aCO2/Ca–vO2 is a complex variable, which depends on several factors. As such, it was a misleading indicator of anaerobic metabolism in hemodilution.Facultad de Ciencias Médica

Venoarterial PCO₂-to-arteriovenous oxygen content difference ratio is a poor surrogate for anaerobic metabolism in hemodilution: an experimental study

Background: The identification of anaerobic metabolism in critically ill patients is a challenging task. Observational studies have suggested that the ratio of venoarterial PCO2 (Pv–aCO2) to arteriovenous oxygen content difference (Ca–vO2) might be a good surrogate for respiratory quotient (RQ). Yet Pv–aCO2/Ca–vO2 might be increased by other factors, regardless of anaerobic metabolism. At present, comparisons between Pv–aCO2/Ca–vO2 and RQ have not been performed. We sought to compare these variables during stepwise hemorrhage and hemodilution. Since anemia predictably produces augmented Pv–aCO2 and decreased Ca–vO2, our hypothesis was that Pv–aCO2/Ca–vO2 might be an inadequate surrogate for RQ. Methods: This is a subanalysis of a previously published study. In anesthetized and mechanically ventilated sheep (n = 16), we compared the effects of progressive hemodilution and hemorrhage by means of expired gases analysis. Results: There were comparable reductions in oxygen consumption and increases in RQ in the last step of hemodilution and hemorrhage. The increase in Pv–aCO2/Ca–vO2 was higher in hemodilution than in hemorrhage (1.9 ± 0.2 to 10.0 ± 0.9 vs. 1.7 ± 0.2 to 2.5 ± 0.1, P < 0.0001). The increase in Pv–aCO2 was lower in hemodilution (6 ± 0 to 10 ± 1 vs. 6 ± 0 to 17 ± 1 mmHg, P < 0.0001). Venoarterial CO2 content difference and Ca–vO2 decreased in hemodilution and increased in hemorrhage (2.6 ± 0.3 to 1.2 ± 0.1 vs. 2.8 ± 0.2 to 6.9 ± 0.5, and 3.4 ± 0.3 to 1.0 ± 0.3 vs. 3.6 ± 0.3 to 6.8 ± 0.3 mL/dL, P < 0.0001 for both). In hemodilution, Pv–aCO2/Ca–vO2 increased before the fall in oxygen consumption and the increase in RQ. Pv–aCO2/Ca–vO2 was strongly correlated with Hb (R2 = 0.79, P < 0.00001) and moderately with RQ (R2 = 0.41, P < 0.0001). A multiple linear regression model found Hb, RQ, base excess, and mixed venous oxygen saturation and PCO2 as Pv–aCO2/Ca–vO2 determinants (adjusted R2 = 0.86, P < 0.000001). Conclusions: In hemodilution, Pv–aCO2/Ca–vO2 was considerably increased, irrespective of the presence of anaerobic metabolism. Pv–aCO2/Ca–vO2 is a complex variable, which depends on several factors. As such, it was a misleading indicator of anaerobic metabolism in hemodilution.Facultad de Ciencias Médica

Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: A prospective study

Introduction: Our goal was to assess the effects of titration of a norepinephrine infusion to increasing levels of mean arterial pressure (MAP) on sublingual microcirculation. Methods: Twenty septic shock patients were prospectively studied in two teaching intensive care units. The patients were mechanically ventilated and required norepinephrine to maintain a mean arterial pressure (MAP) of 65 mmHg. We measured systemic hemodynamics, oxygen transport and consumption (DO2 and VO2), lactate, albumin-corrected anion gap, and gastric intramucosal-arterial PCO2 difference (ΔPCO2). Sublingual microcirculation was evaluated by sidestream darkfield (SDF) imaging. After basal measurements at a MAP of 65 mmHg, norepinephrine was titrated to reach a MAP of 75 mmHg, and then to 85 mmHg. Data were analyzed using repeated measurements ANOVA and Dunnett test. Linear trends between the different variables and increasing levels of MAP were calculated. Results: Increasing doses of norepinephrine reached the target values of MAP. The cardiac index, pulmonary pressures, systemic vascular resistance, and left and right ventricular stroke work indexes increased as norepinephrine infusion was augmented. Heart rate, DO2 and VO2, lactate, albumin-corrected anion gap, and ΔPCO2 remained unchanged. There were no changes in sublingual capillary microvascular flow index (2.1 ± 0.7, 2.2 ± 0.7, 2.0 ± 0.8) and the percent of perfused capillaries (72 ± 26, 71 ± 27, 67 ± 32%) for MAP values of 65, 75, and 85 mmHg, respectively. There was, however, a trend to decreased capillary perfused density (18 ± 10,17 ± 10,14 ± 2 vessels/mm2, respectively, ANOVA P = 0.09, linear trend P = 0.045). In addition, the changes of perfused capillary density at increasing MAP were inversely correlated with the basal perfused capillary density (R2 = 0.95, P < 0.0001). Conclusions: Patients with septic shock showed severe sublingual microcirculatory alterations that failed to improve with the increases in MAP with norepinephrine. Nevertheless, there was a considerable interindividual variation. Our results suggest that the increase in MAP above 65 mmHg is not an adequate approach to improve microcirculatory perfusion and might be harmful in some patients.Facultad de Ciencias Médica

Venoarterial PCO₂-to-arteriovenous oxygen content difference ratio is a poor surrogate for anaerobic metabolism in hemodilution: an experimental study

Background: The identification of anaerobic metabolism in critically ill patients is a challenging task. Observational studies have suggested that the ratio of venoarterial PCO2 (Pv–aCO2) to arteriovenous oxygen content difference (Ca–vO2) might be a good surrogate for respiratory quotient (RQ). Yet Pv–aCO2/Ca–vO2 might be increased by other factors, regardless of anaerobic metabolism. At present, comparisons between Pv–aCO2/Ca–vO2 and RQ have not been performed. We sought to compare these variables during stepwise hemorrhage and hemodilution. Since anemia predictably produces augmented Pv–aCO2 and decreased Ca–vO2, our hypothesis was that Pv–aCO2/Ca–vO2 might be an inadequate surrogate for RQ. Methods: This is a subanalysis of a previously published study. In anesthetized and mechanically ventilated sheep (n = 16), we compared the effects of progressive hemodilution and hemorrhage by means of expired gases analysis. Results: There were comparable reductions in oxygen consumption and increases in RQ in the last step of hemodilution and hemorrhage. The increase in Pv–aCO2/Ca–vO2 was higher in hemodilution than in hemorrhage (1.9 ± 0.2 to 10.0 ± 0.9 vs. 1.7 ± 0.2 to 2.5 ± 0.1, P < 0.0001). The increase in Pv–aCO2 was lower in hemodilution (6 ± 0 to 10 ± 1 vs. 6 ± 0 to 17 ± 1 mmHg, P < 0.0001). Venoarterial CO2 content difference and Ca–vO2 decreased in hemodilution and increased in hemorrhage (2.6 ± 0.3 to 1.2 ± 0.1 vs. 2.8 ± 0.2 to 6.9 ± 0.5, and 3.4 ± 0.3 to 1.0 ± 0.3 vs. 3.6 ± 0.3 to 6.8 ± 0.3 mL/dL, P < 0.0001 for both). In hemodilution, Pv–aCO2/Ca–vO2 increased before the fall in oxygen consumption and the increase in RQ. Pv–aCO2/Ca–vO2 was strongly correlated with Hb (R2 = 0.79, P < 0.00001) and moderately with RQ (R2 = 0.41, P < 0.0001). A multiple linear regression model found Hb, RQ, base excess, and mixed venous oxygen saturation and PCO2 as Pv–aCO2/Ca–vO2 determinants (adjusted R2 = 0.86, P < 0.000001). Conclusions: In hemodilution, Pv–aCO2/Ca–vO2 was considerably increased, irrespective of the presence of anaerobic metabolism. Pv–aCO2/Ca–vO2 is a complex variable, which depends on several factors. As such, it was a misleading indicator of anaerobic metabolism in hemodilution.Facultad de Ciencias Médica

Microcirculatory alterations are more severe in anemic than in ischemic hypoxia

The intestinal mucosal-arterial PCO2 (ΔPCO2) remains remarkably stable in anemic hypoxia suggesting that the villi perfusion is well-maintained. The microcirculation, however, has been insufficiently studied in extreme hemodilution.Facultad de Ciencias Médica

Urinary bladder partial carbon dioxide tension during hemorrhagic shock and reperfusion: an observational study

Introduction: Continuous monitoring of bladder partial carbon dioxide tension (PCO₂) using fibreoptic sensor technology may represent a useful means by which tissue perfusion may be monitored. In addition, its changes might parallel tonometric gut PCO₂. Our hypothesis was that bladder PCO₂, measured using saline tonometry, will be similar to ileal PCO₂ during ischaemia and reperfusion. Method: Six anaesthetized and mechanically ventilated sheep were bled to a mean arterial blood pressure of 40 mmHg for 30 min (ischaemia). Then, blood was reinfused and measurements were repeated at 30 and 60 min (reperfusion). We measured systemic and gut oxygen delivery and consumption, lactate and various PCO₂ gradients (urinary bladder–arterial, ileal–arterial, mixed venous–arterial and mesenteric venous–arterial). Both bladder and ileal PCO2 were measured using saline tonometry. Results: After bleeding systemic and intestinal oxygen supply dependency and lactic acidosis ensued, along with elevations in PCO₂ gradients when compared with baseline values (all values in mmHg; bladder ∆PCO₂ 3 ± 3 versus 12 ± 5, ileal ∆PCO₂ 9 ± 5 versus 29 ± 16, mixed venous–arterial PCO₂ 5 ± 1 versus 13 ± 4, and mesenteric venous–arterial PCO₂ 4 ± 2 versus 14 ± 4; P &lt; 0.05 versus basal for all). After blood reinfusion, PCO₂ gradients returned to basal values except for bladder ∆PCO₂, which remained at ischaemic levels (13 ± 7 mmHg). Conclusion: Tissue and venous hypercapnia are ubiquitous events during low flow states. Tonometric bladder PCO₂ might be a useful indicator of tissue hypoperfusion. In addition, the observed persistence of bladder hypercapnia after blood reinfusion may identify a territory that is more susceptible to reperfusion injury. The greatest increase in PCO₂gradients occurred in gut mucosa. Moreover, the fact that ileal ∆PCO₂ was greater than the mesenteric venous–arterial PCO₂ suggests that tonometrically measured PCO₂ reflects mucosal rather than transmural PCO₂. Ileal ∆PCO₂ appears to be the more sensitive marker of ischaemia.Facultad de Ciencias Médica

Effects of levosimendan and dobutamine in experimental acute endotoxemia : A preliminary controlled study

Objective: To test the hypothesis that levosimendan increases systemic and intestinal oxygen delivery (DO2) and prevents intramucosal acidosis in septic shock. Design: Prospective, controlled experimental study. Setting: University-based research laboratory. Subjects: Nineteen anesthetized, mechanically ventilated sheep. Interventions: Endotoxin-treated sheep were randomly assigned to three groups: control (n = 7), dobutamine (10 μg/kg/min, n = 6) and levosimendan (100 μg/kg over 10 min followed by 100 μg/kg/h, n = 6) and treated for 120 min. Measurements and main results: After endotoxin administration, systemic and intestinal DO 2 decreased (24.6 ± 5.2 vs 15.3 ± 3.4 ml/kg/min and 105.0 ± 28.1 vs 55.8 ± 25.9 ml/kg/min, respectively; p < 0.05 for both). Arterial lactate and the intramucosal–arterial PCO2 difference (∆PCO2) increased (1.4 ± 0.3 vs 3.1 ± 1.5 mmHg and 9 ± 6 vs 23 ± 6 mmHg mmol/l, respectively; p < 0.05). Systemic DO 2 was preserved in the dobutamine-treated group (22.3 ± 4.7 vs 26.8 ± 7.0 ml/min/kg, p = NS) but intestinal DO 2 decreased (98.9 ± 0.2 vs 68.0 ± 22.9 ml/min/kg, p < 0.05) and ∆PCO 2 increased (12 ± 5 vs 25 ± 11 mmHg, p < 0.05). The administration of levosimendan prevented declines in systemic and intestinal DO 2 (25.1 ± 3.0 vs 24.0 ± 6.3 ml/min/kg and 111.1 ± 18.0 vs 98.2 ± 23.1 ml/min/kg, p = NS for both) or increases in ∆PCO2 (7 ± 7 vs 10 ± 8, p = NS). Arterial lactate increased in both the dobutamine and levosimendan groups (1.6 ± 0.3 vs 2.5 ± 0.7 and 1.4 ± 0.4 vs. 2.9 ± 1.1 mmol/l, p = NS between groups). Conclusions: Compared with dobutamine, levosimendan increased intestinal blood flow and diminished intramucosal acidosis in this experimental model of sepsis.Facultad de Ciencias Médica